Select Agents and Toxins Exclusions

The select agent regulations (7 CFR Part 331, 9 CFR Part 121, and 42 CFR Part 73) established a procedure by which an attenuated strain of a select biological agent or toxin that does not pose a severe threat to public health and safety, animal health, or animal products may be excluded from the requirements of the select agent regulations.

Final Rule (October 5, 2012)On October 5, 2012, the final rule excluded any low pathogenic strains of avian influenza virus, any strain of Newcastle disease virus which does not meet the criteria for virulent Newcastle disease virus, all subspecies Mycoplasma capricolum except subspecies capripneumoniae (contagious caprine pleuropneumonia), and all subspecies Mycoplasma mycoides except subspecies mycoides small colony (Mmm SC) (contagious bovine pleuropneumonia), provided that the individual or entity can verify that the agent is within the exclusion category.

In addition, the final rule included the removal of the South American genotypes of Eastern Equine Encephalitis virus (EEE), all Venezuelan Equine Encephalitis virus (VEE) subtypes except IAB and IC, the West African clade of Monkeypox virus and all conotoxins except the sub-class of conotoxins generally called "short, paralytic alpha conotoxins," exemplified by α-conotoxin GI and α-conotoxin MI and containing the following amino acid sequence X1CCX2PACGX3X4X5X6CX7.

To prevent confusion on how an entity should handle samples that have been determined to be within a general taxonomic classification ( e.g ., EEE) but not within a particular genotype or subtype ( e.g., North American EEE virus ), the current general taxonomic listing of HHS and overlap select agents was maintained as opposed to listing a specific strain and adding an exclusion for the strains, subtypes, or pathogenicity levels which are not considered to have the potential to pose a severe threat to public health and safety. When an agent is initially identified by taxonomic classification, it is subject to the select agent regulations until further testing is accomplished to exclude the particular agent by strain, subtype, or pathogenicity level.

North American EEE virus (NA-EEE) genotype strains, which are the strains responsible for human and equine disease, are all genetically very similar to each other (less than 3 percent divergence at the nucleotide level) and can be easily distinguished from South American EEE virus (SA-EEE) genotype strains using diagnostic molecular techniques.

We also note that there are published diagnostic tests that differentiate the Congo Basin clade of Monkeypox virus from the West African clade.

Attenuated Strains of HHS and USDA Select Agents and Toxins

Based upon consultations with subject matter experts and a review of relevant published studies and information provided by the entities requesting the exclusions, the Federal Select Agent Program has determined that the following attenuated strains or less toxic select toxin are not subject to the requirements of the select agent regulations.

An excluded attenuated strain or a select toxin modified to be less potent or toxic will be subject to the regulations if there is any reintroduction of factor(s) associated with virulence, toxic activity, or other manipulations that modify the attenuation such that virulence or toxic activity is restored or enhanced. In addition, attenuated strains or a select toxin modified to be less potent or toxic that are excluded from the requirements of the select agent regulations are not exempt from the requirements of other applicable regulations or guidelines (e.g., NIH guidelines, USDA/APHIS permits, etc.).